gene therapy in treating patients with non-small cell lung cancer that cannot be surgically removed

Conditions: Lung Cancer

Summary: rationale: exposing tumor cells to the p53 gene may improve the body's ability to fight non-small cell lung cancer. purpose: phase i trial to study the effectiveness of gene therapy in treating patients who have non-small cell lung cancer that cannot be surgically removed.

objectives: * evaluate the safety of multiple endobronchial treatments with adenovirus p53 bronchoalveolar lavage of a single lobe of the lung in patients with bronchoalveolar cell lung carcinoma. * evaluate expression of the p53 gene and induction of apoptosis in tumor and normal tissues exposed to the virus in these patients. * evaluate whether transbronchial administration of adenovirus p53 results in improved local tumor control in these patients. outline: this is a dose escalation study. patients undergo biopsy and receive adenovirus p53 by bronchoalveolar lavage on days 1 and 15. patients repeat biopsy on days 3 and 28. if there is evidence of clinical benefit or response without significant toxicity, patients may receive a maximum of 3 courses. treatment beyond 3 courses must be approved by protocol investigator. cohorts of 3 patients are treated at escalating dose levels of adenovirus p53. patients in each cohort are followed for dose limiting toxicity (dlt) for 2 weeks after completion of one course before dose escalation proceeds in subsequent cohorts. if 1 of 3 patients at a dose level experiences dose limiting toxicity (dlt), then 2 additional patients are entered at the same dose level. if more than 1 of 5 patients experience dlt, the previous dose is the maximum tolerated dose (mtd). an additional 10 patients are treated at the mtd. patients are followed every 3 months for the first 2 years, every 6 months for the next 3 years, and annually thereafter. projected accrual: there will be 15 patients accrued into this study over 1 year.

Eligibility criteria:
disease characteristics: * histologically confirmed unresectable non-small cell lung cancer with a growth pattern allowing access to the majority of tumor cells via the airway (e.g., bronchioloalveolar or papillary adenocarcinoma) patient characteristics: age: * 18 and over performance status: * ecog 0-1 life expectancy: * at least 12 weeks hematopoietic: * platelet count greater than 100,000/mm\^3 * prothrombin time and partial thromboplastin time normal hepatic: * bilirubin less than 1.5 mg/dl renal: * creatinine less than 1.5 mg/dl cardiovascular: * no new york heart association class iii or iv heart disease pulmonary: * room air oxygen saturation greater than 90% * fev1 greater than 1.0 l pco2 less than 50 other: * hiv negative * no active systemic viral, bacterial, or fungal infections requiring treatment * no concurrent illness requiring hospitalization or intravenous medication * not pregnant or nursing * effective contraception required of all fertile patients prior concurrent therapy: biologic therapy: * no prior adenovirus gene therapy * at least 2 weeks since any systemic biologic therapy including prior biologic response modifiers and recovered chemotherapy: * at least 2 weeks since any prior systemic chemotherapy and recovered endocrine therapy: * recovered from any prior endocrine therapy radiotherapy: * recovered from any prior radiotherapy surgery: * at least 2 weeks since any surgical procedure requiring anesthesia * at least 4 weeks since prior surgical resection of lung tissues other: * no other concurrent therapy

Keywords: recurrent non-small cell lung cancer stage iiib non-small cell lung cancer stage iv non-small cell lung cancer bronchoalveolar cell lung cancer